Krishnan Arun V, Phoon Richard K S, Pussell Bruce A, Charlesworth John A, Bostock Hugh, Kiernan Matthew C
Prince of Wales Medical Research Institute and Prince of Wales Clinical School, University of New South Wales, Randwick, Sydney, Australia.
Brain. 2006 Jun;129(Pt 6):1585-92. doi: 10.1093/brain/awl099. Epub 2006 Apr 24.
Peripheral neuropathy is present in 65% of patients with end-stage kidney disease (ESKD). No cause is yet established: nerve excitability studies have shown that axons are chronically depolarized, primarily owing to hyperkalaemia, but in vitro studies have suggested a role for axonal Na+/K+ pump dysfunction. To investigate Na+/K+ pump activity in vivo, lower limb ischaemia was induced in five ESKD patients and six healthy controls by a sphygmomanometer cuff, inflated to 200 mm Hg and maintained for 13 min. The peroneal nerve was stimulated at the fibular neck and excitability parameters were recorded from tibialis anterior (TA) and extensor digitorum brevis (EDB) before, during and after the ischaemic period. Baseline excitability studies in ESKD patients demonstrated reductions in threshold electrotonus and superexcitability and increased refractoriness, consistent with membrane depolarization. During ischaemia, threshold increased in ESKD patients [by +23.6 +/- 5.0% (TA); +32.1 +/- 7.3% (EDB)] in contrast to the persistent threshold reduction observed in normal controls [-2.4 +/- 5.2% (TA); -13.0 +/- 8.2% (EDB); P < 0.01]. These changes were accompanied by increased refractoriness and reduced superexcitability in both ESKD and control groups, consistent with ischaemic depolarization. Conversely, there was reduction in strength-duration time constant towards the end of ischaemia. Following release of ischaemia, the marked increase in threshold observed in normal controls was not evident in ESKD patients, but the rapid return of threshold to baseline argues against significant Na+/K+ pump dysfunction. The abnormal pattern of response to ischaemia in the ESKD patients was not fully explained by the hyperkalaemic membrane depolarization and suggests that another dialysable factor affects nerve excitability in ESKD patients, most likely H(+) ions, but that this factor only becomes evident during ischaemia. Blockade of persistent Na+ conductances by H+ would also explain the reduction in strength-duration time constant observed during ischaemia.
65%的终末期肾病（ESKD）患者存在周围神经病变。病因尚未明确：神经兴奋性研究表明轴突长期去极化，主要是由于高钾血症，但体外研究提示轴突钠钾泵功能障碍可能起作用。为了研究体内钠钾泵的活性，对5例ESKD患者和6例健康对照者使用血压计袖带诱导下肢缺血，袖带充气至200 mmHg并维持13分钟。在腓骨小头处刺激腓总神经，并在缺血期之前、期间和之后记录胫前肌（TA）和趾短伸肌（EDB）的兴奋性参数。ESKD患者的基线兴奋性研究显示阈下电紧张和超兴奋性降低，不应期延长，这与膜去极化一致。在缺血期间，ESKD患者的阈值升高[TA升高+23.6±5.0%；EDB升高+32.1±7.3%]，而正常对照者的阈值持续降低[-2.4±5.2%（TA）；-13.0±8.2%（EDB）；P<0.01]。这些变化伴随着ESKD组和对照组不应期延长和超兴奋性降低，这与缺血性去极化一致。相反，在缺血末期强度-时间常数降低。缺血解除后，正常对照者中观察到的阈值显著升高在ESKD患者中不明显，但阈值迅速恢复到基线表明钠钾泵功能没有明显障碍。ESKD患者对缺血的异常反应模式不能完全用高钾性膜去极化来解释，这表明另一种可透析因子影响ESKD患者的神经兴奋性，最有可能是H⁺离子，但这种因子仅在缺血期间才变得明显。H⁺对持续性钠电导的阻断也可以解释缺血期间观察到的强度-时间常数降低。
